1. Field of the Invention
The present invention relates to the solid state chemistry of 3-O-(3′,3′-dimethylsuccinyl)betulinic acid di-N-methyl-D-glucamine salt (“DSB•2NMG”) and its use as an active pharmaceutical agent.
2. Background Art
3-O-(3′,3′-dimethylsuccinyl)betulinic acid di-N-methyl-D-glucamine (“DSB•2NMG”, shown below) is useful in the treatment of HIV and related diseases.
Compound A

U.S. Patent Application No. 60/413,451 discloses 3,3-dimethylsuccinyl betulin and is herein incorporated by reference. Zhu, Y-M. et al., Bioorg. Chem Lett. 11:3115-3118 (2001); Kashiwada Y. et al., J. Nat. Prod. 61:1090-1095 (1998); Kashiwada Y. et al., J. Nat. Prod. 63:1619-1622 (2000); and Kashiwada Y. et al., Chem. Pharm. Bull. 48:1387-1390 (2000) disclose dimethylsuccinyl betulinic acid (“DSB”) and dimethylsuccinyl oleanolic acid. Esterification of the 3′ carbon of betulin with succinic acid produced a compound capable of inhibiting HIV-1 activity (Pokrovskii, A. G. et al., Gos. Nauchnyi Tsentr Virusol. Biotekhnol. “Vector,” 9:485-491 (2001)).
U.S. patent application Ser. No. 11/081,802 herein incorporated by reference discloses salts of DSB, including N-methyl-D-glucamine salts, their preparation, pharmaceutical compositions thereof, and methods of use thereof in the treatment of HIV. The preparation of DSB•2NMG described in Ser. No. 11/081,802 involves the slow addition of diethyl ether to a methanolic solution of DSB•2NMG to produce a white solid. U.S. patent application Ser. No. 11/081,802 describes certain DSB•2NMG as crystalline, however, upon further spectral inspection, it has been determined that material produced in accordance with the procedure in paragraph [0088] of Ser. No. 11/081,802 (or paragraph [0074] of U.S. Publication No. US 2005/0239748) is actually amorphous DSB•2NMG as confirmed by x-ray powder diffraction data depicted herein.
As crystalline compounds demonstrate differing chemical and physical properties relative to amorphous compounds, the identification of crystalline forms of DSB•2NMG would represent an advance in the pharmaceutical arts. Synthetic processes useful to prepare such crystalline forms of DSB•2NMG would represent a further advance in the art. Methods of using such crystalline forms of DSB•2NMG would represent yet another advance in the art.